title: Clearance of asymptomatic P. falciparum Infections Interacts with the number of clones to predict the risk of subsequent malaria in Kenyan children.
abstract: BACKGROUND
  Protective immunity to malaria is acquired after repeated infections in endemic areas. Asymptomatic multiclonal P. falciparum infections are common and may predict host protection. Here, we have investigated the effect of clearing asymptomatic infections on the risk of clinical malaria.
  
  
  METHODS
  Malaria episodes were continuously monitored in 405 children (1-6 years) in an area of moderate transmission, coastal Kenya. Blood samples collected on four occasions were assessed by genotyping the polymorphic P. falciparum merozoite surface protein 2 using fluorescent PCR and capillary electrophoresis. Following the second survey, asymptomatic infections were cleared with a full course of dihydroartemisinin.
  
  
  RESULTS
  Children who were parasite negative by PCR had a lower risk of subsequent malaria regardless of whether treatment had been given. Children with ≥ 2 clones had a reduced risk of febrile malaria compared with 1 clone after clearance of asymptomatic infections, but not if asymptomatic infections were not cleared. Multiclonal infection was associated with an increased risk of re-infection after drug treatment. However, among the children who were re-infected, multiclonal infections were associated with a shift from clinical malaria to asymptomatic parasitaemia.
  
  
  CONCLUSIONS
  The number of clones was associated with exposure as well as blood stage immunity. These effects were distinguished by clearing asymptomatic infection with anti-malarials. Exposure to multiple P. falciparum infections is associated with protective immunity, but there appears to be an additional effect in untreated multiclonal infections that offsets this protective effect.
authors.affiliation: Infectious Diseases Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anne
authors.initials: A
authors.lastname: Liljander
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
authors.forename: Jedidah
authors.initials: J
authors.lastname: Mwacharo
authors.forename: Oscar
authors.initials: O
authors.lastname: Kai
authors.forename: Edna
authors.initials: E
authors.lastname: Ogada
authors.forename: Norbert
authors.initials: N
authors.lastname: Peshu
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.forename: Anna
authors.initials: A
authors.lastname: Färnert
mesh_terms: D058345:Asymptomatic Infections; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells / Q000166:cytology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007223:Infant; D007630:Kenya; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000209:etiology* / Q000469:parasitology / Q000635:transmission; D008297:Male; D018512:Parasitemia / Q000175:diagnosis; D010963:Plasmodium falciparum / Q000166:cytology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D012307:Risk Factors